Genetically altered and defined cell lines for transplantation in animal models of Parkinson's disease

Parkinson's disease is the functional central nervous system (CNS) disorder for which the goals of transplantation are most clearly defined. It is generally accepted that many of the manifestations of this disorder are related to a single missing circuit link: the dopaminergic innervation of the striatum. L-dopa has been very effective in the treatment of Parkinson's disease. It is thought that systemically administered L-dopa is decarboxylated locally forming dopamine, which then interacts with receptor sites in the corpus striatum. The efficacy of L-dopa treatment is generally limited by side effects, especially on–off phenomena, which result in a gradual narrowing of the therapeutic window and eventually a nearly complete loss of useful effects. The dramatic initial efficacy of L-dopa as well as newer methods such as lisuride infusion pumps, however, strongly suggests that alleviation of most symptoms of Parkinson's disease can be accomplished by diffuse, nonsynaptic release of dopamine into the denervated areas. In animal models, as well as for human trials, the goal of transplantation is to replace the missing striatal dopaminergic innervation, whether this is accomplished via production of a new dopaminergic innervation secretion of dopamine or other catecholamine from the grafts or trophic actions on endogenous host system. The chapter examines the possibilities for mimicking the effects with intracerebral grafts of defined and genetically altered cell lines.